Design, synthesis and biological evaluation of a simplified fluorescently labeled discodermolide as a molecular probe to study the binding of discodermolide to tubulin

Abstract

The design, synthesis, and biological evaluation of a simplified fluorescently labeled discodermolide analogue possessing a dimethylaminobenzoyl fluorophore has been achieved. Stereoselective Suzuki coupling, Horner–Wadsworth–Emmons reaction or the Wittig reaction comprised the key tactics for its construction. The analogue exhibited qualitatively similar activity to paclitaxel in a tubulin assembly assay, and it can thus be used as a fluorescent molecular probe to explore the local environment of the discodermolide binding site on tubulin. The results of fluorescence measurements on the tubulin-bound analogue are reported.